1.Field of the Invention
This invention relates generally to a non-invasive method of identifying and quantifying constituents of arterial plaque, and specifically to a method using protons NMR spectroscopy to indicate accumulation of lipids within the walls of human arterial blood vessels and within the aortic walls.
2. Prior Art
Atherosclerosis is the leading cause of death and debility in the United States and other Western industrialized nations. Its presence is often first identified by the occurrence of heart attack, stroke, renal failure, or sudden death. Nearly one of every three Americans can expect to suffer from the consequences of this disease. In particular, coronary artery disease due to atherosclerosis takes the lives of approximately 550,000 Americans each year--an enormous toll. Put in economic terms, the cost to the United States alone has been estimated to exceed 60 billion dollars annually.
The early lesions in blood vessel walls are marked by clinically silent accumulations of cholesterol and cholesteryl esters, as well as triglycerides, phospholipids, and various lipoproteins. The lipids deposited between the intima and media of the arterial wall are believed to originate mainly from serum low density lipoproteins (LDL), which transport cholesterol within the body in the form of cholesteryl esters. Epidemiological studies, drug trials, and biochemical studies have all pointed to the implication of cholesterol and saturated fats of dietary and endogenous origin in the etiology of atherosclerosis. Dietary polyunsaturated fats, by contrast, are associated with reduced LDL cholesterol levels and lower incidence of cardiovascular disease. Lipids accumulating within the arterial wall may initiate the atherosclerotic process through injury of the blood vessel inner surface, followed by release of chemotactic substances, attraction of monocytes which ingest further lipids to become foam cells, and agglutination of platelets. Production of growth factors can then stimulate smooth muscle cells to migrate to the damaged area, which differentiate into fibroblasts leading to eventual calcification. The clinical end results of atherosclerosis are caused by thrombosis or occlusion of the diseased vessels due to arterial plaque, thereby reducing or eliminating the supply of blood to key tissues and organs, such as the heart or brain.
Beyond this, little is known with certainty of the means by which lipids accumulate within the arterial wall, a process beginning often in childhood or early adolescence. As a result, strategies for prevention of atherosclerosis within the population at large have met with limited success. The availability of noninvasive methods for monitoring of atherogenesis in conjunction with more effective regimens for treatment of susceptible individuals would represent a significant step forward. In particular, it seems worthwhile to pursue development of methods for accurately identifying and quantifying the lipid constituents of atherosclerotic plaque within human arterial vessels, which mark early and potentially reversible disease stages. Previous investigators have shown that high-resolution, carbon-13 (.sup.13 C) NMR spectra can be acquired from in tact (ex vivo) atherosclerotic lesions of human and animal origin, Hamilton et al., "Lipid Dynamics in Human Low-Density Lipoproteins and Human Aortic Tissue with Fibrous Plaques", J. BIOL. CHEM. 254, 5435-5441 (U.S.A. 1979); Cushley et al., "A .sup.13 C and .sup.31 P Nuclear Magnetic Resonance of Lipid Dispersions from Human Aorta", CAN. J. BIOCHEM. 58, 206-212 (Canada 1979). Others have obtained high-resolution .sup.13 C and proton (.sup.1 H) NMR spectra from serum lipoproteins, Steim et al., "Structure of Human Serum Lipoproteins", SCIENCE 162, 909-911 (U.S.A. 1968); Leslie et al., "Nuclear Magnetic Resonance Studies of Serum Low Density Lipoproteins (LDL2)", CHEM. PHYS. LIPIDS 3, 152-158 (Holland 1969); Finer et al., "NMR Studies of Pig- Low and High- Density Serum Lipoproteins", BIOCHIM. BIOPHYS. ACTA 176, 320-337 (Holland 1975); Sears, "Temperature-Dependent 13C Nuclear Magnetic Resonance Studies of Human Serum Low Density Lipoproteins", BIOCHEMISTRY 15, 4151-4157 (U.S.A. 1976); Hamilton et al., "Lipid Dynamics in Human Low-Density Lipoproteins and Human Aortic Tissue with Fibrous Plaques", J. BIOL. CHEM. 254, 5435-5441 (U.S.A. 1979). However, proton NMR studies of arterial tissue have not been reported.